Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha ...(SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.
Core decompression (CD) is an important method for the treatment of osteonecrosis of the femoral head (ONFH). Few articles investigate the influence of core decompression on outcomes of ONFH. This ...study was carried out to observe the safety and effectiveness of core decompression in the treatment of ONFH.
A comprehensive literature search of databases including PubMed, Embase, and Cochrane Library was performed to collect the related studies. The medical subject headings used were "femur head necrosis" and "Core decompression." The relevant words in title or abstract included but not limited to "Osteonecrosis of the Femoral Head," "femoral head necrosis," "avascular necrosis of femoral head," and "ischemic necrosis of femoral head." The methodological index for nonrandomized studies was adopted for assessing the studies included in this review.
Thirty-two studies included 1865 patients (2441 hips). Twenty-one studies (1301 hips) using Ficat staging standard, 7 studies (338hips) using Association Research Circulation Osseous (ARCO) staging standard, and University of Pennsylvania system for staging avascular necrosis (UPSS) staging criteria for 4 studies (802 hips). All the studies recorded the treatment, 22 studies (1379 hips) were treated with core decompression (CD) alone, and 7 studies (565 hips) were treated with core decompression combined with autologous bone (CD Autologous bone). Nine subjects (497 hips) were treated with core decompression combined with autologous bone marrow (CD Marrow). Twenty-seven studies (2120 hips) documented the number of conversion to total hip replacement (THA), and 26 studies (1752hips) documented the number of radiographic progression (RP). Twenty-one studies recorded the types of complications and the number of cases, a total of 69 cases. The random-effect model was used for meta-analysis, and the results showed that the overall success rate was 65%. The rate of success showed significant difference on the outcomes of different stages. The rate of success, conversion to THA, and radiographic progression showed significant difference on the outcomes of ONFH using different treatments.
Core decompression is an effective and safe method of treating ONFH. The combined use of autologous bone or bone marrow can increase the success rate. For advanced femoral head necrosis, the use of CD should be cautious. High-quality randomized controlled trials and prospective studies will be necessary to clarify the effects of different etiology factors, treatments, and postoperative rehabilitation. Until then, the surgeon can choose core decompression to treat ONFH depending on the patient's condition.
I Meta-analysis.
Noncoding RNAs (ncRNAs) were initially thought to be transcriptional byproducts. However, recent advances of ncRNAs research have increased our understanding of the importance of ncRNA in gene ...regulation and disease pathogenesis. Consistent with these developments, liver fibrosis research is also experiencing rapid growth in the investigation of links between ncRNAs and the pathology of this disease. The initial focus was on studying the function and regulation mechanisms of microRNAs (miRNAs). However, recently, elucidation of the mechanisms of long noncoding RNAs (lncRNAs) and lncRNA‐mediated liver fibrosis has just commenced. In this review, we emphasize on abnormal expression of lncRNAs in liver fibrosis. Furthermore, we also discuss that the interaction of lncRNAs with miRNAs is involved in the regulation of the expression of protein‐coding genes in liver fibrosis. Recent advances in understanding dysregulated lncRNAs expression and the lncRNAs–miRNAs interaction in liver fibrosis will help for developing new therapeutic targets and biomarkers of liver fibrosis.
We emphasize on abnormal expression of long noncoding RNAs (lncRNAs) in liver fibrosis. Furthermore, we also discuss that the interaction of lncRNAs with micoRNAs is involved in the regulation of the expression of protein‐coding genes in liver fibrosis.
Advancements in complexity, complex systems, and the intelligence sciences, particularly smart city technologies, have shown great potential in aiding to ease traffic congestion. The overall approach ...and the main ideas in building smart transportation for smart cities, particularly ACP (artificial system, computational experiment, and parallel execution)-based parallel transportation management and control systems (PTMS), are presented. PTMS can be expanded to the new generation of intelligent transportation systems. The main components of the proposed architecture include social signal and social traffic, ITS clouds and services, agent-based traffic control, and transportation knowledge automation. Some technical details of these components are discussed. Finally, one case study is introduced, and the effectiveness is analyzed.
Reconstruction of massive bone defects is challenging for orthopaedic clinicians, especially in cases of severe trauma and resection of tumors in various locales. Autologous iliac crest bone graft ...(ICBG) is the “gold standard” for bone grafting. However, the limited availability and complications at donor sites resulted in seeking other options like allografts and bone graft substitutes. Demineralized bone matrix (DBM) is a form of allograft using acidic solution to remove mineral components, while leaving much of the proteinaceous components native to bone, with small amounts of calcium‐based solids, inorganic phosphates, and some trace cell debris. It is an osteoconductive and osteoinductive biomaterial and is approved as a medical device for use in bone defects and spinal fusion. To pack consistently into the defect sites and stay firmly in the filling parts, DBM products have various forms combined with biocompatible viscous carriers, including sponges, strips, injectable putty, paste, and paste infused with chips. The present review aims to summarize the properties of various kind of viscous carriers and their clinical use combined with DBM in commercially available products. Given DBM'mercially available products. Given DBM;s long clinical track record and commercial accessibility in standard forms, opportunities to further develop and validate DBM as a versatile bone biomaterial in orthopaedic repair and regenerative medicine contexts are attractive.
Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems and society in ...general. ARDs are characterized by the progressive deterioration of tissues and organs over time, eventually leading to tissue and organ failure. To date, there are no effective interventions to prevent the progression of ARDs. Hence, there is an urgent need for new treatment strategies. Ferroptosis, an iron-dependent cell death, is linked to normal development and homeostasis. Accumulating evidence, however, has highlighted crucial roles for ferroptosis in ARDs, including neurodegenerative and cardiovascular diseases. In this review, we a) summarize initiation, regulatory mechanisms, and molecular signaling pathways involved in ferroptosis, b) discuss the direct and indirect involvement of the activation and/or inhibition of ferroptosis in the pathogenesis of some important diseases, and c) highlight therapeutic targets relevant for ARDs.
The intrusion detection system can distinguish normal traffic from attack traffic by analyzing the characteristics of network traffic. Recently, neural networks have advanced in the fields of natural ...language processing, computer vision, intrusion detection and so on. In this paper, we propose a unified model combining Multiscale Convolutional Neural Network with Long Short-Term Memory (MSCNN-LSTM). The model first employs Multiscale Convolutional Neural Network(MSCNN) to analyze the spatial features of the dataset, and then employs Long Short-Term Memory (LSTM) Network to process the temporal features. Finally, the model employs the spatial-temporal features to perform the classification. In the experiment, the public intrusion detection dataset, UNSW-NB15 was employed as experimental training set and test set. Compared with the model based on the conventional neural networks, the MSCNN-LSTM model has better accuracy, false alarm rate and false negative rate.
Background Prosthesis-related complications, after knee reconstruction with endoprosthesis during operation for tumors around the knee, remain an unresolved problem which necessitate a revision or ...even an amputational surgery. The purpose of the current study was to identify significant risk factors associated with implant failure, and establish a novel model to predict survival of the prosthesis in patients operated with endoprostheses for tumor around knee. Methods We retrospectively reviewed the clinical database of our institution for patients who underwent knee reconstruction due to tumors. A total of 203 patients were included, including 123 males (60.6%) and 80 (39.4%) females, ranging in age from 14 to 77 years (mean: 34.3 + or - 17.3 years). The cohort was randomly divided into training (n = 156) and validation (n = 47) samples. Univariable COX analysis was used for initially identifying potential independent predictors of prosthesis survival with the training group (p < 0.150). Multivariate COX proportional hazard model was selected to identify final significant prognostic factors. Using these significant predictors, a graphic nomogram, and an online dynamic nomogram were generated for predicting the prosthetic survival. C-index and calibration curve were used for evaluate the discrimination ability and accuracy of the novel model, both in the training and validation groups. Results The 1-, 5-, and 10-year prosthetic survival rates were 94.0, 90.8, and 83.0% in training sample, and 96.7, 85.8, and 76.9% in validation sample, respectively. Anatomic sites, length of resection and length of prosthetic stem were independently associated with the prosthetic failure according to multivariate COX regression model (p<0.05). Using these three significant predictors, a graphical nomogram and an online dynamic nomogram model were generated. The C-indexes in training and validation groups were 0.717 and 0.726 respectively, demonstrating favourable discrimination ability of the novel model. And the calibration curve at each time point showed favorable consistency between the predicted and actual survival rates in training and validation samples. Conclusions The length of resection, anatomical location of tumor, and length of prosthetic stem were significantly associated with prosthetic survival in patients operated for tumor around knee. A user-friendly novel online model model, with favorable discrimination ability and accuracy, was generated to help surgeons predict the survival of the prosthesis. Keywords: Limb salvage, Prognostic factor, Tumor endoprostheses, Nomogram
•A novel CFRP-hollow section steel tube (CFRP-HSST) composite member with a thick-walled section at each side was proposed to suppress premature end-debonding of CFRP.•A tensile test on 8 CFRP-HSST ...composite member specimens (i.e., 4 CHS and 4 SHS composite member specimens) was carried out.•A greater load-carrying capacity and ductility of the proposed CFRP-HSST composite member can be achieved with the increase in the number of CFRP layers.•The validated FE model can reasonably simulate the adhesive damage evolution, and subsequent parametric analysis was performed.
Carbon fiber reinforced polymer (CFRP) is extensively utilized to strengthen steel structures. However, the premature debonding failure of CFRP inhibits its validity in strengthening tensile steel structures. Accordingly, the introduction of a thick-walled hollow section steel tube located at both ends of the CFRP-hollow section steel tube (CFRP-HSST) composite member was developed for the strengthening of tensile members. The steel tube in the novel composite member is constituted of a middle thin-walled section and a pair of thick-walled sections at each end providing anti-debonding resistance. The strengthening efficiency of the novel composite member under axial tensile loading was experimentally investigated by 8 specimens, comprising 4 circular cross section and 4 square cross section composite members. It was found that the presence of thickened section could achieve the stress gradient of CFRP and distribute the adhesive's interfacial shear stress. In addition, the finite element model (FEM) of the proposed CFRP-HSST composite member was developed and examined the adhesive damage distribution and evolution, and subsequently, a parametric analysis was carried out. The results indicate that the novel CFRP-HSST composite member can be regarded as an efficient strengthening solution for suppressing the premature debonding failure as well as increasing the strengthening efficiency.
Ischemic brain injury results from complicated cellular mechanisms. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA) ...and mechanical recanalization. Therefore, a better understanding of ischemic brain injury is needed for the development of more effective therapies. Disruption of ionic homeostasis plays an important role in cell death following cerebral ischemia. Glutamate receptor-mediated ionic imbalance and neurotoxicity have been well established in cerebral ischemia after stroke. However, non-NMDA receptor-dependent mechanisms, involving acid-sensing ion channel 1a (ASIC1a), transient receptor potential melastatin 7 (TRPM7), and Na(+)/H(+) exchanger isoform 1 (NHE1), have recently emerged as important players in the dysregulation of ionic homeostasis in the CNS under ischemic conditions. These H(+)-sensitive channels and/or exchangers are expressed in the majority of cell types of the neurovascular unit. Sustained activation of these proteins causes excessive influx of cations, such as Ca(2+), Na(+), and Zn(2+), and leads to ischemic reperfusion brain injury. In this review, we summarize recent pre-clinical experimental research findings on how these channels/exchangers are regulated in both in vitro and in vivo models of cerebral ischemia. The blockade or transgenic knockdown of these proteins was shown to be neuroprotective in these ischemia models. Taken together, these non-NMDA receptor-dependent mechanisms may serve as novel therapeutic targets for stroke intervention.
PDF
